One of the basic tenets of anticancer chemotherapy is that increased tumor exposure to drug should result in increased tumor response. One method currently being used to increase drug exposure of malignant brain tumors is by intracarotid infusion. Although intracarotid infusion increases drug delivery, systemic toxicity, not brain toxicity, frequently limits the tolerable dose. A means of extracting the drug from the blood after one passage through the brain, and before the high concentration of drug reaches the general circulation, should allow dose escalation to levels which provide increased tumor response. The following have been demonstrated. 1) A pilot study of 4 patients treated with intracarotid BCNU during extracorporeal hemoperfusion of the jugular venous blood demonstrated that the drug exposure of the body could be reduced by 56-87% by channeling the blood extracorporeally at 300 ml/min through a hemoperfusion cartridge for drug extraction. The pharmacokinetic advantage (ratio of brain exposure to body exposure) compared to intravenous infusion of the same dose was 21-55:1. 2) Drug streaming during intracarotid delivery results in maldistribution of the infused agent with the potential of delivering very high (toxic) concentrations of drug to some regions of the brain, while other areas receive minimal drug. Drug streaming is probably the cause of focal encephalomalacia following intracarotid infusion of BCNU. 3) A dye dilution study of intracarotid infusion of indocyanine green demonstrated that the recovery of substances from the jugular blood after intracarotid infusion is linearly related to the rate of aspiration of the blood from the jugular blood. This suggests that the amount of an injected drug which can be removed from blood before the blood is returned to the body is dependent on the rate at which blood is withdrawn from the jugular vein. 4) Extracorporeal circulation of the jugular blood for drug removal during intracarotid infusion of cis-platinum resulted in tumor exposures 5-15 flow greater than the exposure of the remainder for the body.